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Title:
CONFIGURABLE MICROFLUIDIC DEVICE AND METHOD
Document Type and Number:
WIPO Patent Application WO/2006/104467
Kind Code:
A1
Abstract:
A microfluidic device (10) has a fluid channel (20) and a blocker (22), removable by heating, occluding the fluid channel (20). The device (10) may have a substrate (14) and a cover (12) covering the substrate. The cover (12) may have a groove, formed by heating the cover (12) with a die biased against the cover (12), forming the fluid channel (20). A section of the cover (12) may be heated and deformed to block the channel (20). A heating element (30) may be formed on the substrate (14) for heating the blocker (22) or the section of the cover (12) to be deformed. The device may have interconnected fluid channels (20) and gates or valves, which may include such a blocker (22) removable by heating, for directing fluid flow through the fluid channels.

Inventors:
Lee, Ki Bang (993 Bukit Timah Road, #03-10 Maplewoods Condominium, Singapore 1, 58963, SG)
Hsieh, Tseng-ming (5 Pine Grove, #02-05 Astor Green, Singapore 1, 59759, SG)
Application Number:
PCT/SG2006/000073
Publication Date:
October 05, 2006
Filing Date:
March 28, 2006
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (20 Biopolis Way, #07-01 Centros, Singapore 8, 13866, SG)
Lee, Ki Bang (993 Bukit Timah Road, #03-10 Maplewoods Condominium, Singapore 1, 58963, SG)
Hsieh, Tseng-ming (5 Pine Grove, #02-05 Astor Green, Singapore 1, 59759, SG)
International Classes:
B81B3/00; B01L3/00; F15C5/00
Foreign References:
FR2856046A1
GB2414059A
US6048734A
US6102897A
US6679279B1
US20020194909A1
US6702256B2
US6382254B1
Attorney, Agent or Firm:
YU SARN AUDREY & PARTNERS (190 Middle Road, #12-04, Singapore 9, 18897, SG)
Download PDF:
Claims:
WHAT IS CLAIMED IS:
1. A microfluidic device, comprising: a substrate; a cover layer on said substrate; said substrate and said cover layer defining a fluid channel enclosed therebetween, said fluid channel extending between an entrance and an exit and having a crosssectional dimension below 1 mm; a blocker placed in said fluid channel between said entrance and said exit and occluding said fluid channel, said blocker removable through said fluid channel by heating at a temperature at which the integrity of said device is preserved to allow a fluid to flow from said entrance to said exit through said fluid channel.
2. The microfluidic device of claim 1 , further comprising a heating element adjacent said blocker for heating said blocker.
3. The microfluidic device of claim 2, wherein said heating element comprises an electrode placed on one of said substrate and said cover layer.
4. The microfluidic device of claim 3, wherein said electrode comprises a metal electrode.
5. The microfluidic device of any one of claims 1 to 4, wherein said blocker comprises a material which sublimes at a temperature below 200 0C.
6. The microfluidic device of any one of claims 1 to 5, wherein said blocker comprises a material which melts at a temperature from 70 to 200 °C.
7. The microfluidic device of any one of claims 1 to 6, wherein said blocker comprises a material selected from naphthalene, paradichlorobenzene, camphor, menthol, wax, and plastic.
8. The microfluidic device of claim 1 , wherein said blocker comprises naphthalene.
9. The microfluidic device of any one of claims 1 to 8, wherein said cross sectional dimension is from 1 to 500 microns.
10. The microfluidic device of any one of claims 1 to 9, further comprising a plurality of interconnected channels, and a plurality of gates respectively disposed within said channels for directing fluid flow through selected ones of said channels, one of said gates comprising said blocker.
11. The microfluidic device of claim 10, wherein at least one of said gates is disposed at an intersection of at least two of said channels.
12. The microfluidic device of claim 10 or claim 11 , wherein each one of said gates is settable to one of a closed state and an open state.
13. The microfluidic device of any one of claims 1 to 12, further comprising at least one fluid chamber in fluid communication with said fluid channel.
14. The microfluidic device of any one of claims 1 to 13, wherein said cover layer has a surface defining a groove, said surface of said cover layer and said substrate facing each other thus defining said fluid channel.
15. The microfluidic device of claim 14, wherein said cover layer is transparent.
16. The microfluidic device of claim 14 or claim 15, wherein said cover layer comprises a thermoplastic.
17. The microfluidic device of any one of claims 1 to 16, further comprising a valve for regulating fluid flow through said channel.
18. A method of configuring a fluidic device, comprising: providing a microfluidic device having a fluid channel and a blocker occluding said fluid channel; and heating said blocker to remove said blocker through said fluid channel to allow a fluid to flow through said fluid channel.
19. The method of claim 18, wherein said blocker comprises a material which sublimes at a temperature below 200 0C.
20. The method of claim 18, wherein said blocker comprises a material which melts at a temperature from 70 to 200 0C.
21. The method of any one of claims 18 to 20, wherein said blocker comprises a material selected from naphthalene, paradichlorobenzene, camphor, menthol, wax, and plastic.
22. The method of claim 18, wherein said blocker comprises naphthalene.
23. The method of any one of claims 18 to 22, wherein said heating comprises energizing a heating element in said fluidic device adjacent said blocker to heat said blocker.
24. The method of any one of claims 18 to 22, wherein said heating comprises irradiating said blocker to impart energy to said blocker .
25. A method of configuring a microfluidic device comprising a substrate covered by a cover layer, said substrate and cover layer defining a fluid channel, said method comprising: heating a portion of said cover layer pressed toward said substrate to deform said portion of said cover layer such that fluid flow within said fluid channel is blocked by said deformed portion of said cover layer.
26. The method of claim 25, wherein said cover layer comprises a thermoplastic.
27. The method of claim 25 or 26, wherein said heating comprises irradiating said portion of said cover layer.
28. A method of forming a microfluidic device, comprising: forming a heating element on a first layer; and covering said first layer with a second layer having a surface defining a groove, said surface facing said first layer, thus defining a fluid channel between said first and second layers, a section of said fluid channel adjacent said heating element.
29. The method of claim 28, further comprising forming said groove in said second layer by heating said second layer while biasing a die against said surface of said second layer.
30. The method of claim 29, wherein said die comprises a metal wire.
31. The method of any one of claims 28 to 30, further comprising depositing a blocker material in said fluid channel adjacent said heating element for occluding said fluid channel.
32. The method of claim 31 , further comprising heating said blocker material to form a blocker occluding said fluid channel.
33. A method of forming a fluidic device, comprising: heating a cover, layer with a die biased against a surface of said cover layer, to form a groove in said cover layer; and covering a substrate with said cover layer, said surface of said cover layer facing said substrate such that a fluid channel is defined between said substrate and said cover layer.
34. The method of claim 33, wherein said fluid channel has a crosssectional dimension below 1 mm.
35. The method of claim 33 or claim 34, further comprising forming a gate for blocking fluid flow through said fluid channel.
36. The method of claim 35, wherein said forming a gate comprises disposing a blocker in said fluid channel to occlude said fluid channel, said blocker removable by heating.
37. The method of claim 36, wherein said blocker comprises naphthalene.
38. The method of any one of claims 35 to 37, wherein said forming a gate comprises heating a portion of said cover layer and pressing said portion toward said substrate to deform said portion of said cover layer such that fluid flow within said fluid channel is blocked by said deformed portion of said cover layer.
39. The method of any one of claims 33 to 38, further comprising forming at least one fluid chamber in fluid communication with said fluid channel.
40. The method of any one of claims 33 to 39, comprising forming a plurality of fluid channels defined by said cover layer and substrate.
41. The method of claim 40, wherein said plurality of fluid channels are interconnected.
42. The method of claim 41 , comprising forming a plurality of gates within said fluid channels for directing fluid flow through selected ones of said fluid channels, each one of said gates settable from a first state to a second state.
43. The method of any one of claims 33 to 42, wherein said die comprises a metal wire.
44. The method of any one of claims 33 to 43, wherein said cover layer comprises a thermoplastic.
45. A programmable microfluidic device, comprising: a substrate and a cover layer defining a plurality of interconnected fluid channels enclosed therebetween; and a plurality of gates disposed in said fluid channels, each one of said gates settable to one of an open state and a closed state, at least one of said gates comprising a blocker removable through one or more of said channels by heating, whereby said microfluidic device is programmable by selectively setting at least one of said gates to a selected one of said open and closed states.
46. The programmable microfluidic device of claim 45, wherein at least one of said gates comprises a portion of said cover layer adjacent a section of said fluid channels, said portion deformable by heat and pressure for blocking fluid flow through said section.
47. The programmable microfluidic device of claim 45 or claim 46, wherein at least one of said fluid channels is in fluid communication with an input, and at least one of said fluid channels is in fluid communication with an output.
48. The programmable microfluidic device of any one of claims 45 to 47, wherein said fluid channels form a Cartesian network.
49. A method comprising: providing a microfluidic device having a fluid channel enclosed" between a substrate and a cover layer covering said substrate, said fluid channel extending between an entrance and an exit; and forming a blocker at a preselected location in said fluid channel between said entrance and said exit to occlude said fluid channel, said blocker removable through said fluid channel by heating at a temperature at which the integrity of said microfluidic device is preserved to allow a fluid to flow through said fluid channel.
50. The method of claim 49, wherein said forming comprises disposing a blocker material in said fluid channel adjacent said location and heating said blocker material to melt said blocker material to occlude said fluid channel.
51. The method of claim 50, wherein said blocker material has a melting temperature from 70 to 200 0C.
52. The method of claim 50 or claim 51 , wherein said heating comprises energizing a heating element in said microfluidic device adjacent said blocker material to heat said blocker material.
53. The method of claim 50 or claim 51 , wherein said heating comprises irradiating said blocker material to impart energy to said blocker material.
54. The method of any one of claims 49 to 53, wherein said blocker comprises a material selected from the group of naphthalene, paradichlorobenzene, camphor, menthol, wax, and plastic.
Description:
CONFIGURABLE MICROFLUIDIC DEVICE AND METHOD

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. provisional application No. 60/666,730 filed March 31 , 2005, the contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention relates generally to fluidic devices, and more particularly to configurable microfluidic devices.

BACKGROUND OF THE INVENTION

[0003] Microfluidic devices or systems are useful and have wide applications in many fields such as life science, biological, chemical, and medical research and industry. For example, they have been used for medical diagnosis and treatment and have been incorporated into biosystems, lab-on- a chip devices, integrated micro-devices and the like.

[0004] Typically, a microfluidic device has one or more fluid channels formed in a substrate, as well as reservoirs, chambers, pumps, gates or valves, electrodes, and other components. Common substrate materials are glass, polymers and silicon. Microfluidic devices are generally fabricated using conventional semiconductor techniques, such as photolithography and etching. For example, fluid cavities such channels, reservoirs, mixers, reaction chambers can be formed within laminated layers using these semiconductor techniques, such as described in U.S. Patent No. 6,136,212 to C. H. Mastrangelo et al. ("Mastrangelo"), issued October 24, 2000, the contents of which are incorporated herein by reference.

[0005] However, the existing devices and fabrication techniques have some drawbacks. One problem is that the conventional devices are inconvenient to use. For example, once fabricated, it is difficult for a user to customize or configure the device, such as altering a fluid path, adding or

removing a fluid control component in the device. Another problem is that the conventional fabrication processes, such as photolithography and etching, may involve the use of chemical materials that pollute the environment. A further problem is that the conventional processes are generally complicated and expensive to carry out. For example, they typically require expensive clean-room equipments and complicated mask processing.

[0006] Accordingly, there is a need for a configurable microfluidic device. There is also a need for an inexpensive method of fabricating fluidic devices.

SUMMARY OF THE INVENTION

[0007] Therefore, in accordance with an aspect of the present invention, there is provided a microfluidic device. The microfluidic device comprises a substrate and a cover layer on the substrate. The substrate and the cover layer define a fluid channel enclosed therebetween. The fluid channel extends between an entrance and an exit and has a cross-sectional dimension below 1 mm. A blocker is placed in the fluid channel between the entrance and the exit and occludes the fluid channel. The blocker is removable through the fluid channel by heating at a temperature at which the integrity of the device is preserved to allow a fluid to flow from the entrance to the exit through the fluid channel.

[0008] In a further aspect of the present invention, there is provided a method of configuring a fluidic device. In this method, a microfluidic device having a fluid channel and a blocker occluding the fluid channel is provided. The blocker is heated to be removed to allow a fluid to flow through the fluid channel.

[0009] In another aspect of the present invention, there is provided a method of configuring a microfluidic device comprising a substrate covered by a cover layer, the substrate and cover layer defining a fluid channel. In this method, a portion of the cover layer pressed toward the substrate is heated to deform the portion of the cover layer such that fluid flow within the fluid channel is blocked by the deformed portion of the cover layer.

[0010] In another aspect of the present invention, there is provided a method of forming a microfluidic device. In this method, a heating element is formed on a first layer. The first layer is covered with a second layer having a surface defining a groove, the surface facing the first layer. The first and second layers thus define a fluid channel therebetween. A section of the fluid channel is adjacent the heating element.

[0011 ] In another aspect of the present invention, there is provided a method of forming a fluidic device. In this method, a cover layer with a die biased against a surface of the cover layer is heated to form a groove in the cover layer. A substrate is covered with the cover layer. The surface of the cover layer faces the substrate such that a fluid channel is defined between the substrate and the cover layer.

[0012] In another aspect of the present invention, there is provided a programmable microfluidic device. The device comprises a substrate and a cover layer defining a plurality of interconnected fluid channels enclosed therebetween. The device also comprises a plurality of gates disposed in the fluid channels, each one of the gates settable to one of an open state and a closed state, at least one of the gates comprising a blocker removable through one or more of the channels by heating. The microfluidic device is programmable by selectively setting at least one of the gates to a selected one of the open and closed states.

[0013] In yet another aspect of the present invention, there is provided a method in which a microfluidic device is provided. The device has a fluid channel enclosed between a substrate and a cover layer covering the substrate. The fluid channel extends between an entrance and an exit. A blocker is formed at a pre-selected location in the fluid channel between the entrance and the exit to occlude the fluid channel. The blocker is removable through the fluid channel by heating at a temperature at which the integrity of the device is preserved to allow a fluid to flow through the fluid channel.

[0014] Other aspects and features of the present invention will become apparent to those of ordinary skill in the art upon review of the following

description of specific embodiments of the invention in conjunction with the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In the figures, which illustrate, by way of example only, embodiments of the present invention,

[0016] FIG. 1A is a top plan view of a configurable microfluidic device;

[0017] FIG. 1 B is a front cross-sectional view of the microfluidic device of FIG. 1 A taken along the line B-B;

[0018] FIG. 1C is a top plan view of the device of FIG. 1A after configuration;

[0019] FIGS. 1 D and 1 E are partial cross-sectional views of the device of FIG. 1C taken along the line D-D, respectively during and after further configuration;

[0020] FIG. 2 is a partial cross-sectional view of a variation of the device of FIG. 1 A before and after configuration;

[0021] FIG. 3A is a cross-sectional view of a film and a wire before heating;

[0022] FIG. 3B is a cross-sectional view of the film of FIG. 3A after heating;

[0023] FIG. 3C is a perspective view of the film of FIG. 3B;

[0024] FIG. 3D a perspective view of a substrate;

[0025] FIG. 3E is a perspective view of the film of FIG. 3C and the substrate of FIG. 3D before lamination;

[0026] FIG. 3F is a cross-sectional view of the device formed from the film and substrate of FIG. 3E;

[0027] FIG. 4 is a schematic diagram illustrating a process of forming a fluidic device;

[0028] FIG. 5 is a schematic diagram illustrating the operation of a blocker machine;

[0029] FIG. 6A is a schematic diagram of a microfluidic device; and

[0030] FIGS. 6B to 6E are schematic diagrams of the device of FIG. 6A after respective configuration.

DETAILED DESCRIPTION

[0031] FIGS. 1 A and 1 B illustrate a configurable microfluidic device 10, exemplary of embodiments of the present invention. Device 10 includes a cover layer, polymer film 12, and a substrate 14 which is covered or laminated with film 12. Film 12 and substrate 14 define fluid chambers 16 and 18 and a fluid channel 20 connecting chambers 16 and 18. Channel 20 is enclosed between film 12 and substrate 14. Chamber 16 may serve as the fluid entrance for channel 20, and chamber 18 may serve as the fluid exit for channel.20. A blocker 22 is initially disposed within channel 20 between its entrance and exit, thus occluding channel 20, thus blocking fluid communication between chambers 16 and 18. Thus, blocker 22 serves as a gate for controlling fluid flow within channel 20. An optional heating element such as electrode 30 is disposed on substrate 14, the use of which will become clear below. Optionally, a conductive wire 32, such as aluminum or gold wire, may also be placed on substrate 14 for connecting electrode 30 to a power source (not shown).

[0032] Film 12 is transparent. In alternative embodiments, film 12 may be translucent or opaque. Substrate 14 may be transparent, translucent or opaque. Polymer film 12 and substrate 14 may be formed of any suitable material. For example, film 12 may be formed of a thermoplastic. Film 12 may also be a gel or poly(dimethylsiloxane) (PDMS) film, or the like. It may be advantageous in some applications if film 12 has one or more of the following properties: transparent, bendable, thin, inexpensive, biocompatible, and

waterproof. It is also advantageous if a hole can be easily formed in film 12 such as by punching. Materials suitable for spin-coating may also be advantageous if the film is to be formed by spin-coating.

[0033] Substrate 14 may be made of any suitable material. For example, Substrate 14 may be made from silicon, polymer, glass, plastic, semiconductor materials, or the like. Substrate 14 may also be made of metal when conductive elements such as electrode 30 and wire 32 are omitted, or, optionally, when insulation is provided to electrically insulate electrode 30, wire 32 and any other conductive elements from the conductive body of substrate 14.

[0034] Chambers 16 and 18 may have any desired shape or dimension depending on the intended use. They may be formed in any suitable manner. For example, they may be formed as described below or according to a conventional technique.

[0035] Channel 20 may also have any desired shape or dimension. Generally, channel 20 may be a microchannel having a cross-sectional dimension below 1 mm. For example, channel 20 may have a diameter, width or depth from about 1 micron to about 500 microns. Channel 20 may be formed in accordance with an embodiment of the present invention, as will be described below. The entrance and exit of channel 20 may have different shapes in different embodiments.

[0036] Blocker 22 can be made of a heat sensitive material and can be in the solid or liquid phase. A solid blocker may be advantageous in various applications. On heating, blocker 22 can sublime, melt or otherwise dissolve, and can thus be removed. However, blocker 22 should not be removable under normal working conditions by the fluid pressure within channel 20. As can be understood, blocker 22 should be removable at a temperature at which the integrity of device 10 can be preserved, i.e., without destroying or damaging device 10, any component or structure on device 10. Materials that are solid at room temperature but sublimes or melts at a temperature slightly higher than room temperature would be suitable for many applications.

Materials that can sublime or melt at temperatures between 70 to 200 0 C may be advantageous, as they can be used for a wide range of applications. Materials that can sublime quickly at a temperature below 120 0 C can be particularly advantageous. For example, naphthalene can be a suitable blocker material in some applications. Naphthalene is solid at room temperature and has a melting point of about 80 0 C. Naphthalene is also insoluble in water, which can be advantageous. As will be appreciated, naphthalene can sublime and be removed quickly when heated. Naphthalene is commercially available, such as from Sigma™. As can be understood, naphthalene can sublime slowly at room temperature under atmospheric pressure. Slight sublimation may be acceptable as long as the blocker material is not substantially removed before it is to be removed. To reduce sublimation, device 10 may be stored under high pressure, such as being encapsulated in capsules filled with high pressure nitrogen. In different embodiments, more stable block materials may be used. Other suitable blocker materials include paradichlorobenzene, camphor, menthol, wax, and the like.

[0037] Th& blocker material may also be selected depending on the way it is to be removed. If it is to be removed using an adjacent heater such as electrode 30, a sublimable material may be advantageous. If it is to be removed by, for example, using a laser beam as will be further discussed below, a non-sublime material such as a plastic may be used.

[0038] As can be appreciated, blocker 22 should also be resistant to fluid introduced into chamber 16 or 18 and channel 20. For example, a material that will react with or dissolve in the fluid may not be suitable. Thus, suitable blocker materials may vary depending on the application and the fluids to be used.

[0039] Electrode 30 can be made of any suitable material, such as a metal. For example, it may be made of gold. An electrical wire may be connected to electrode 30 for connection to a power source.

[0040] Device 10 may be fabricated using any suitable techniques,

including the methods disclosed herein. Suitable conventional techniques may be used for fabricating device 10 or its components.

[0041] Device 10 may have other components or features not shown in the figures, depending on the application and intended use. For example, chambers 16 and 18 may be in fluid communication with a fluid source or exhaust. A fluid pump, electrodes, or a heating element (not shown) may be provided on or connected to device 10.

[0042] The materials for fabricating device 10 may be selected depending on the particular fabrication process used and/or intended use. For example, when device 10 is to be used for biochemical analysis, the materials may need to be biocompatible.

[0043] In operation, blocker 22 may be left in tact so that it serves as a "closed" gate. In this case, no fluid will flow through channel 20 between chambers 16 and 18. For example, chambers 16 and 18 can be fluid reservoirs each holding a reagent fluid for a test reaction and it may be desirable to delay the reaction between the two fluids until a certain event has occurred or a certain condition has been satisfied, such as when the device is placed at a test site or cell culturing in one of the chambers has been completed.

[0044] However, when fluid communication between chambers 16 and 18 is desired, blocker 22 may be removed by heating. When heated, blocker 22 is vaporized or liquefied and can be either transported out of channel 20 or dispersed in channel 20, as can be understood by persons skilled in the art. In either case, channel 20 is no longer blocked. As can be appreciated, blocker 22 can be considered removed when a fluid can flow through channel 20 and it is not necessary to completely displace the entire blocker 20.

[0045] Blocker 22 can be removed at a temperature at which film 12 or substrate 14 is not substantially softened so that the integrity of device 10 is preserved. For example, a naphthalene blocker can be removed at a temperature below about 80 0 C. Naphthalene blockers can be removed quickly at temperatures from about 85 to about 90 0 C. As illustrated in FIG.

1C, when blocker 22 is removed, the gate is set, or "configured", to an "open" state and a fluid flow can flow through channel 20.

[0046] Electrode 30 may be conveniently used as a heating element for heating and thus removing blocker 22. An electrical current may be induced in electrode 30 to energize the heating element so as to heat blocker 22. To ensure that device 10 will not be over-heated during removal of blocker 22, the heating temperature may be controlled, such as with an electronic control device. As can be appreciated, a proportional- integral-derivative (PID) temperature control instrument such as LFI3751 ™ provided by Wavelength Electronics Inc.™ may be used such as connected to electrode 30 for this purpose.

[0047] In different embodiments, one or more heating elements may be placed on either the substrate or the cover layer, or both. When an electrode is used as a heating element, the electrode may be embedded in the device.

[0048] It is possible to re-block fluid communication between chambers 16 and 18 after blocker 22 has been removed. For example, when film 12 is made of a suitable thermoplastic, a portion 24 of film 12 adjacent a section of channel 20 (as indicated by dashed lines in FIG. 1 D) may be heated and pressed against substrate 14, such as with a soldering iron 25 as illustrated in FIG. 1 D. When film 12 is cooled again, portion 24 of film 12 is persistently deformed and blocks fluid flow though channel 20, as illustrated in FIG. 1 E. Portion 24 may also be deformed with a high energy beam such as a laser beam or a beam of high energy particles, as can be understood by persons skilled in the art.

[0049] As can be understood, blocker 22 may also be removed using another suitable technique. For example, it is not necessary to provide a heating element within device 10 and an external heating source may be used for removing blocker 22.

[0050] In an alternative embodiment, blocker 22 may be irradiated to impart energy to it. A highly focused energy beam such as a laser beam or an ultrasonic wave can be used to remove a blocker as illustrated in FIG. 2.

Device 10' is similar to device 10 except that there is no heating element adjacent the blocker. In particular, a fluid channel 20' between a cover 12' and a substrate 14' is initially occluded by blocker 22', as shown at the top of FIG. 2. An irradiation beam, indicated by the dotted lines, may be focused on blocker 22', for example, through cover 12' to melt, vaporize or ablate blocker 22', as can be readily understood by persons skilled in the art. Thus, blocker 22' can be removed to open up channel 20' to allow a fluid (not shown) to flow through, as shown at the bottom of FIG. 2.

[0051] When channel 20' is open, cover 12' may also be irradiated to deform it so as to block channel 20'. It can be irradiated with a laser to heat it while pressed towards substrate 14'. Alternatively, cover 12' may be irradiated with a beam of energized particles to impart energy and apply sufficient pressure to it so as to deform it.

[0052] As now can be appreciated, devices 10, 10' and 40 can be conveniently configured or customized, such as by a user, by selectively blocking or unblocking the fluid channel thereon. A person skilled in the art can readily appreciate that there are many possible applications for configurable fluidic devices such as those described herein. For different applications, in alternative embodiments of the fluidic devices more than one fluid channels and more than one blockers may be provided to control fluid flow, as will be further illustrated below.

[0053] FIGS. 3A to 3F illustrates a process for forming device 10, exemplary of embodiments of the present invention.

[0054] As shown in FIG. 3A, a cover layer such as film 12 is heated with a die such as a metal wire 26 biased against a surface 13 of film 12. Film 12 and wire 26 can be heated in a laminator, such as the laminator model PDA3- 330C™ provided by Alliance Advanced Pte Ltd.™ Wire 26 may be pressed against surface 13 by gravity or otherwise. Wire 26 may have a diameter of about 0.6 mm. The diameter can vary depending on the desired dimensions for the resulting fluid channel. Wire 26 may have any desired cross-sectional shape, such as a circular, rectangular, oval, or polygon shape.

[0055] As can be appreciated, in different embodiments, the die can have a different shape and configuration, but should have an external shaping surface for shaping a cavity in film 12. For example, instead of a wire, the die may have a larger body with a generally flat surface, on which a ridge is formed for shaping groove 28. When interconnected channels are to be formed, the die may be formed of correspondingly interconnected wires. For different applications, the die may also include one or more portions shaped for forming other types of cavities on the cover layer, such as wells, reservoirs, reaction chambers, and the like.

[0056] The resulting film 12 has a groove 28 formed on surface 13, as illustrated in FIGS. 3B and 3C. FIG. 3B is a cross-sectional view of film 12 taken along the line 3B-3B in FIG. 3C, after heating and removal of wire 26.

[0057] A substrate 14 is also provided. As illustrated in FIG. 3D, a heating element such as a gold electrode 30 is deposited on a surface 15 of substrate 14. Electrode 30 may be deposited using a conventional technique such as screen printing or chemical evaporation. For example, substrate 14 may be formed from a commercially available material, such as a Perfex™ crystal clear laminating film with a polyester base, sold by GMP Co. Ltd. Substrate may be 100 microns thick. Optionally, aluminum wire 32 may also be placed on substrate 14 for connecting electrode 30 to a power source (not shown). Cavities 34 and 36 are made in substrate 14 on surface 15. Cavities 34 and 36 may be formed using any suitable technique. For example, they may be formed with a hole puncher.

[0058] As illustrated in FIGS. 3E and 3F, film 12 and substrate 14 are then laminated or bonded together to form device 10, with surfaces 13 and 15 facing each other defining the fluid channel 20. The lamination or bonding may be carried out using any suitable process.

[0059] Electrode 30 is disposed adjacent a section of channel 20 where a gate is, or is to be, formed. For example, blocker 22 may be deposited in this section. Blocker 22 may be formed in channel 20 in any suitable manner.

[0060] Another exemplary process of forming a fluidic device, such as

device 40 having a blocker 22', is illustrated in FIG. 4. As shown, a metal layer 42 is first deposited on substrate 14'. Layer 42 may be made of Cr or Au, or both. Layer 42 is then patterned, such as by etching or another suitable technique, to form heater electrode 30' at a pre-selected location on substrate 14', which can function similarly as electrode 30 in device 10 of FIG. 1A. A blocker layer 44 is next deposited on substrate 14' and electrode 30', and then patterned into a block 46 adjacent electrode 30'. Block 46 may also be formed directly without first forming layer 44. Blocker layer 44 can be made of a material that either sublimes or melts at low temperature. A cover film 12' is bounded to substrate 14' defining a fluid microchannel 20' around block 46. At this stage, a small gap 48 may still exist between film 12' and block 46 so that a fluid may flow through microchannel 20'. Block 46 can be heated until melting, such as with heater 30' or otherwise. The liquid phase blocker material can form blocker 22' due to surface tension, which fills gap 48. As can be appreciated, blocker 22' can occlude microchannel 20'. If the blocker material is a sublimation material, the heating can be carried out under high pressure to reduce loss of blocker material. As can be appreciated, blocker 22' can be conveniently formed at any time after film 12' and substrate 14' are bounded together, by inducing an electrical current in electrode 30' to energize the heating element. For example, a voltage may be applied across electrode 30' to induce the current.

[0061] In alternative embodiments, a blocker may also be formed by manually insert a blocker material, such as sublimation powder or film, into the channel.

[0062] The process of installing or removing the blocker may also be automated.

[0063] Fig. 5 illustrates an exemplary process for blocking or unblocking a fluid channel of a fluidic device, such as device 60, with the use of a blocker machine 62.

[0064] Device 60 has a fluid channel 64 which has two branch channels 64A and 64B. Initially, channels 64A and 64B are unblocked as shown at the

top of FIG. 5. As indicated by the solid arrows, device 60 may be fed through blocker machine 62 as indicated by the solid arrows. Blocker machine 62 is adapted to install a blocker 66 in a channel of device 60, such as channel 64A as shown. After passing through blocker machine 62, a previous unblocked channel such as channel 64A on device 60 can be blocked by a blocker such as blocker 66, as shown at the bottom of FIG. 5. A blocker material may be either pre-deposited in channel 64A, such as described above and illustrated in FIG. 3, or injected into channel 64A in blocker machine 62. Upon being heated, the blocker material may form blocker 66, such as described above. Blocker machine 62 may also install blockers in any other suitable manner.

[0065] Alternatively, blocker machine 62 may be adapted to heat and remove a blocker in a fluidic device. For example, device 60 with blocker 66 may be fed through such a blocker machine 62 to remove blocker 66 from device 60 as indicated by the dotted arrows in FIG. 5.

[0066] . Optionally, blocker machine 62 can be constructed to both remove and install blockers on fluidic devices.

[0067] Blocker machine 62 can be readily constructed by persons skilled in the art after reading this paper. For example, the blocker machine may have a heater (not shown) or a laser beam (not shown) for heating a blocker material and thus removing/installing a blocker in a channel. The process shown in FIG. 5 may be automated. Multiple fluidic devices may be transported to and from blocker machine 62 using a conveyer or another transport system including a robotic system. Blocker machine 62 may also be adapted to remove or install multiple blockers and may be able to selectively remove/install blockers in a fluidic device.

[0068] As can be understood, devices 10, 10' and 40 can also be fabricated using conventional processes used in fabrication of microfluidic devices.

[0069] The advantages of a configurable microfluidic device described herein can be further appreciated from the device 50, exemplary of embodiments of the present invention, which is only partially and

schematically shown in FIGS. 6A to 6E. Device 50 has multiple fluid channels 52 and configurable gates 54. One or more channels 52 may be in fluid communication with a fluid input (not shown) such as through the gate 54 marked as "A", and one or more channels 52 may be in fluid communication with a fluid output (not shown), such as through the gate 54 marked as "B". The numbers of channels and gates may vary in different embodiments. In alternative embodiments, some intersections may have no gate.

[0070] In an exemplary embodiment, each gate 54 includes a blocker disposed at the corresponding intersection so that it blocks fluid flow between the channels 52 connected to the gate through the intersection. The blocker for gate 54 can be made of the same material for blocker 22, and can be similarly formed. The blocker, as blocker 22, can be removed by heating. Thus, each gate 54 is initially in a closed state and can be set to an open state, as described above with reference to device 10. In alternative embodiments, one or more gates 54 may be initially in an open state and is settable to a closed state, as described above.

[0071] As depicted, channels 52 are interconnected and form a Cartesian network. Gates 54 are disposed at the intersections of the channels. The arrangement of channels 52 and gates 54 may vary depending on the application and intended use. The number of channels 52, their shape and dimensions, their cross-linkage can also vary. For example, one or more channels 52 may be in the shape of a storage chamber, reaction chamber, a reservoir, a filter, or the like. It is also not necessary that all channels 52 are interconnected. Gates 54 may be positioned away from the intersections. Positioning gates at the intersections may be advantageous because the number of gates required may be reduced.

[0072] Device 50 is a programmable device and can be programmed or configured for performing a variety of functions, as illustrated in FIGS. 6B to 6E. As depicted in FIGS. 6B to 6E, open gates are indicated with open circles and closed gates are indicated with a cross in the circle; the open fluid channels 50 are indicated with solid lines and closed channels are indicated with dashed lines. In some cases, not all intersections have gates and those

intersections that have no gates are not circled.

[0073] As illustrated in FIG. 6B, device 50 can be configured to alter fluid flow path within channels 52 by selectively setting one or more gates 54 to a different state. Thus, device 50 can be used for controlling fluid path. As shown, a fluid may be received at the input gate marked "A" and output through the output gate marked "B", flowing in the direction indicated by the arrow.

[0074] FIG. 6C illustrates configuring device 50 to control reaction time. A valve 56 may be provided which can be controlled by a user or a controller to selectively open or close at different times. In operation, a fluid containing reagents may be received at the input gate marked "A" and output through valve 56 along the flow path indicated by the solid line. During flow, the reagents may react with each other. The length of the flow path can be increased or decreased by selectively setting respective gates to open or closed states. As the reaction time during flow through the path is dependent on the length of the path, the reaction time may be adjusted by altering the flow path. Further, valve 56 can be controlled to control the duration the fluid stays in the channel, and thus the reaction time of the reagent chemicals. When valve 56 is used to control reaction time, the flow path length may be adjusted to control the amount of reacting fluid received in the path.

[0075] In FIG. 6D, device 50 is configured for mixing two fluids. In operation, two fluids are respectively received at the two input gates marked "A". The two fluids merge at a controllable valve 58, which can be controlled by a user or a controller to selectively open or close at different times so as to control whether and when a mixture of two fluids will be allowed to flow through to the output gate marked "B".

[0076] In FIG. 6E, device 50 is configured for dividing a fluid into two streams. The fluid may be received at the input gate marked "A" and output at two output gates marked "A".

[0077] In FIGS. 6A to 6E, the channel section at each gate marked "A" may be considered as an entrance and the channel section marked at each

gate marked as "B" may be considered as an exit. Further, each intersection on device 50 may be considered as either an entrance or an exit, depending on the fluid flow direction and the fluid channel section involved.

[0078] Of course, the above examples are illustrative only and a person skilled in the art can readily appreciate and understand that configurable or programmable devices can have any number of different configurations and can be used in other manners.

[0079] As can be appreciated and understood, configurable devices as described above can have wide applications in many different fields and industries. For example, embodiments of the present invention may have applications in life science, biological and biochemical research, clinical diagnosis and treatment, drug analysis, and the like. More specifically, they can be used in capillary electrophoresis, high throughput screening, biotechnological assaying such as immunoassaying, isoelectric focusing, flow cytometry, analyte detection, polymerase chain reaction (PCR) amplification, DNA analysis, cell manipulation, cell separation, cell patterning, chemical gradient formation, and the like. Embodiments of the present invention can be incorporated into different fluidic devices such as lab-on-a-chip devices and micro electromechanical systems (MEMS). Such devices can be used to measure molecular diffusion, fluid viscosity, pH, chemical binding, and enzyme reaction kinetics. Many other applications of the embodiments of the present invention can be readily understood and conceived by persons skilled in the art upon reading this paper.

[0080] Advantageously, fluidic devices can be formed according to aspects of the present invention at low cost. The devices can be reliable, customizable and biocompatible. It is also possible to form other components, such as batteries and biosensors, on a fluidic device by lamination, in accordance with aspects of the present invention.

[0081 ] Other features, benefits and advantages of the embodiments described herein not expressly mentioned above can be understood from this description and the drawings by those skilled in the art.

[0082] The contents of each reference cited above are hereby incorporated herein by reference.

[0083] Of course, the above described embodiments are intended to be illustrative only and in no way limiting. The described embodiments are susceptible to many modifications of form, arrangement of parts, details and order of operation. The invention, rather, is intended to encompass all such modification within its scope, as defined by the claims.